Our lab is focused on the design and application of statistical and computational algorithms to elucidate global epigenetic and transcriptional regulatory mechanism, by interpreting and integrating data from ChIP-chip/seq, DNA methylation, Nucleosome positioning, Alternative splicing and Motif finding.

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My research deals with the Front Tracking method in which surfaces of discontinuity are given explicit computational degrees of freedom, supplementing the continuous solution values at regular grid points to provide high quality and high resolution numerical solutions to physical problems. We have developed the concept of Front Tracking into a robust simulation code, parallelized, tested on multi-physics, and used for production simulations in three dimensions.

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An elaborate system of epigenetic and transcription regulation is responsible for the morphological and behavioral complexity in higher eukaryotes. This regulatory system consists of diverse trans-acting protein factors, cis-acting regulatory DNA sequences and the underlying epigenomic background, such as histone modifications, DNA methylation and Nucleosome localizations. Recently, Chromatin ImmunoPrecipitation coupled with whole genome tiled microarray (ChIP-chip) and/or next-generation sequencing (Solexa, SOLiD and 454) has evolved as a powerful and unbiased technique to study this genome-wide regulatory system. The application of this technology to multiple factors and/or in multiple conditions allows biologists to study how transcription is differentially regulated in a combinatorial manner. However, it also poses great challenges for the development of effective algorithms, the key link between massive raw data and biological hypotheses.

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Two tracking methods, called grid-free and grid-based tracking, have been used to describe the three dimensional interface propagation and its topological bifurcation. The former is a pure Lagrangian method in which the interface propagation and redistribution are independent of the underlying Eulerian grid. This method is more accurate in the propagation of the interface position, but it is not robust in resolving the interface geometry and the topological bifurcations. The latter is just the opposite. That is, it is robust in resolving the interface topology, but poses a larger error in interface propagation. Its handling of the interface topology is through the reconstruction of the interface on Eulerian mesh blocks similar to that by Lorensen and Cline. Since topological changes are frequent in the computation of fluid interface instabilities, the grid-based tracking method has been used for most simulations, after an initial time interval. In a new development, we have combined these two methods to form the locally grid based tracking method, or LGB. In this method, we use Lagrangian algorithm for propagation and confine the topological bifurcation in small boxes to do Eulerian bifurcation. The use of Eulerian method is reduced to minimum and only used when and where the topological bifurcation is needed.

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We developed a series of algorithms to reliably detect and annotate ChIP-enriched regions using Next-generation sequencing (MACS; Genome Biology 2008) and Affymetrix whole-genome tiling arrays, including 1) Model-based Analysis of Tiling-arrays (MAT; PNAS 2006) and a hidden Markov model (Bioinformatics 2005) for ChIP-region detection, 2) extreme MApping of OligoNucleotide (xMAN; BMC Genomics 2008) for microarray probe mapping, 3) Cis-regulatory Element Annotation System (CEAS; NAR 2006) for ChIP-region annotation. Since the inception in early 2006, they have been adopted by hundreds of academic users and are now considered as the ChIP-chip data analysis standard in many labs. We worked with ENCODE consortium to systematically analyze the performance variability introduced in ChIP-chip protocols, array platforms, and analysis methods (Genome Res. 2008). Furthermore, we are also in close collaboration with several labs on identifying global regulation targets of several key transcription factors, including Estrogen Receptor (Cell 2005; Nature Genetics 2006); Androgen Receptor (Molecular Cell 2007; Cell 2009) and FoxA1 (Cell 2008).

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In addition, we have recently introduced a conservative front tracking algorithm. It preserves conservation properties of the system by enforcing conservation for all grid cells, including the ones cut by the front. We have extended the grid-based tracking into an interface separating multiple components. The most useful interface, after the case of two components in a block, is an interface separating three material components in a block. For such an interface in three dimensions, after rotation and commutation, the block interface can be attributed to 57 isomorphically distinct cases. We have built 57 subroutines for the front tracking code to handle all these cases.

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We are currently collaborating with many BCM laboratories to use the Next generation sequencing to study 1) Transcription factor binding and histone modifications (ChIP-seq); 2) DNA methylation at single nucleotide resolution (Bisulfite-seq); 3) Nucleosome remodeling (Mnase-seq); 4) Alternative splicing (RNA-seq). My laboratory also plays an important role in the BCM Epigenomics Data Analysis and Coordination Center for a five-year [http://nihroadmap.nih.gov/epigenomics/referenceepigenomeconsortium.asp NIH Roadmap Epigenomics Program].

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Automatic mesh refinement (AMR) is another powerful tool to concentrate computational power in regions of computational difficulty. Block-structured adaptive Cartesian mesh refinement was proposed and developed by Berger and Colella. Our Front Tracking code has adopted the AMR by inter-operating with the Overture code developed by the Lawrence Livermore National Laboratory.

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[http://sites.google.com/a/bcm.edu/lilab/ Lab Intranet]

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The Front Tracking method has been applied to the research and computation of various physical and scientific problems including the study of acceleration driven fluid interface instabilities, the computation of supernova formation, the simulation of spray in diesel fuel-injection jet and migration of white blood cells.

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[http://openwetware.org/wiki/Li_Lab openwetware]

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Revision as of 09:45, 30 August 2010

Recent Presentations

Upcoming Conferences

Research Interests

My research deals with the Front Tracking method in which surfaces of discontinuity are given explicit computational degrees of freedom, supplementing the continuous solution values at regular grid points to provide high quality and high resolution numerical solutions to physical problems. We have developed the concept of Front Tracking into a robust simulation code, parallelized, tested on multi-physics, and used for production simulations in three dimensions.

Two tracking methods, called grid-free and grid-based tracking, have been used to describe the three dimensional interface propagation and its topological bifurcation. The former is a pure Lagrangian method in which the interface propagation and redistribution are independent of the underlying Eulerian grid. This method is more accurate in the propagation of the interface position, but it is not robust in resolving the interface geometry and the topological bifurcations. The latter is just the opposite. That is, it is robust in resolving the interface topology, but poses a larger error in interface propagation. Its handling of the interface topology is through the reconstruction of the interface on Eulerian mesh blocks similar to that by Lorensen and Cline. Since topological changes are frequent in the computation of fluid interface instabilities, the grid-based tracking method has been used for most simulations, after an initial time interval. In a new development, we have combined these two methods to form the locally grid based tracking method, or LGB. In this method, we use Lagrangian algorithm for propagation and confine the topological bifurcation in small boxes to do Eulerian bifurcation. The use of Eulerian method is reduced to minimum and only used when and where the topological bifurcation is needed.

In addition, we have recently introduced a conservative front tracking algorithm. It preserves conservation properties of the system by enforcing conservation for all grid cells, including the ones cut by the front. We have extended the grid-based tracking into an interface separating multiple components. The most useful interface, after the case of two components in a block, is an interface separating three material components in a block. For such an interface in three dimensions, after rotation and commutation, the block interface can be attributed to 57 isomorphically distinct cases. We have built 57 subroutines for the front tracking code to handle all these cases.

Automatic mesh refinement (AMR) is another powerful tool to concentrate computational power in regions of computational difficulty. Block-structured adaptive Cartesian mesh refinement was proposed and developed by Berger and Colella. Our Front Tracking code has adopted the AMR by inter-operating with the Overture code developed by the Lawrence Livermore National Laboratory.

The Front Tracking method has been applied to the research and computation of various physical and scientific problems including the study of acceleration driven fluid interface instabilities, the computation of supernova formation, the simulation of spray in diesel fuel-injection jet and migration of white blood cells.